dr.

Shinta Nareswari
 Hyperthyroidism in children is primarily linked to
Grave’s disease (99% of the cases).

 The disease can occur at any age with a peak in

prevalence during adolescence.

 It can also occur in very young children under 5 years

of age (about 10% of cases).

 There is a strong predominance of cases in females.

 Graves’ disease is more common in children with
other autoimmune diseases (linked mainly to Type
1 Diabetes, Turner’s syndrome, Down Syndrome,
DiGeorge Syndrome) and in children with a family
history of autoimmune thyroid disease.

 Inherited forms account for 15 to 20% of cases.

 The epidemiology of Graves’ disease in children
is poorly understood and has primarily been
studied in northern Europe and China.

 In Northern Europe  0,1 per 100.000 person-

years in young children and 3 per 100.000
person-years in adolescents.

 In Hong Kong  14 per 100.000 person-years.

 In USA  1 per 10.000

 In France  4.8 per 100.000

 The majority of pediatric patients with
Graves’ disease display classic signs of
hyperthyroidism  tachycardia, goiters,
diarrhea or increased appetite with or without
weight loss.

 Initial signs are mostly non-specific, such as

asthenia, sleep disorders, thermophobia,
irritability, emotionality, tremors, palpitations
and behavioral disorders accompanied by
decreased academic performance.
 Goiters are presen at diagnosis in more than
half of cases and are firm and homogeneous
hyper-vascularised and of variable size.

 Eye damage is not uncommon in children but

occurs less frequently in adults and is also
less severe in its appearance. Exophthalmos
is rare and oculomotor damage and optic
neuropathy are very uncommon.
 The initial clinical presentation is often severe (>3/4 of
cases), especially in young children.

 The spesific symptoms observed in children include:

◦ Cardiac problems manifesting as badly tolerated tachycardia,
hypertension, systolic murmurs due to mitral insufficiency caused by
mitral prolapse
◦ Accelerated growth rate with increasing bone maturation, in case of
late diagnosis
◦ Neurological problems with abnormal involuntary spastic movements
◦ Behavioral problems: hyperactivity, concentration disorders, change
in behavior and drop-off in academic performance
◦ Neuropsychiatric problems including anxiety and depression,
agitation, opposition, aggressiveness or even confussion
◦ Bone problems, (as in adults) such as decrease in bone mineralization
(usually cortical bone) and which is corrected with hyperthyroidism
treatment.
 In view of the high sensitivity of antibodies,
differential diagnoses of Graves’ disease
should be considered in the absence of TSH
receptor antibodies in children with
hyperthyroidism:
◦ McCune-Albright syndrome (MCA)
◦ Toxic adenoma
◦ Hashitoxicosis
◦ De Quervain’s subacute thyroiditis
◦ Iodine-induced hyperthyroidism
◦ False hyperthyroidism
 Drug therapy is the first-line treatment for Graves’ disease
in children.

 It can result in the disease being completely cured, but it

often has to be administered over a prolonged period.

 The efficacy and tolerability of drugs should be monitored

throughout the duration of treatment.

 The only treatments prescribed for children are derivatives

of imidazole, carbimazole or thiamazole.

 Due to the greater (though still low) frequency of

hepatotoxicity occuring in children, propylthiouracil is
contraindicated for children.
4.1. Course of treatment
 The initial dosage of carbimazole or thiamazole is 0.4
to 0.8 mg/kg/d (0.3 to 0.6 mg/kg for thiamazole), up
to a limit of 30 mg/d.

 Treatment usually leads to euthyroidism within a few

weeks (generally 2 to 6 weeks).

 Monitoring of drug tolerance and biological thyroid

balance (fT4, fT3, and TSH) is usually required after 2
weeks, after 1 month and on a monthly basis
thereafter, until normalization of TSH. When TSH is
normalized, clinical and biological monitoring (only
TSH) can take place on a quarterly basis.
4.1. Course of treatment
 Treatment is administered in 1 to 2 doses per
day. Administration on 1 dose per day may
result in better patient compliance.

 When normal function of the thyroid is

achieved, treatment can be gradually reduced
by 30-50% to a minimum effective
maintenance dose that usually amounts to
between 5 and 15 mg/d in children.
4.1. Course of treatment
 If the symptoms are severe (tachycardia) or
are poorly tolerated, additional treatment
with beta-blockers (atenolol 1 to 2 mg/kg in
2 dose, or propanolol 1 to 2 mg/kg in 2 to 3
doses), during the first 2-4 weeks of
treatment with antithyroid agents may be
proposed until the normalization of thyroid
hormone is achieved.
4.2. Side effects
 Agranulocytosis (even rarer: pancytopenia)
complications occur very rarely (0.2%).
Hyperthyroidism itself may be responsible for
mild neutropenia or for a moderate rise in
transaminases. Liver damage is rare.

 Minor side effects such as urticaria, arthralgia

and rashes occur frequently in children, in 5-
25% of cases.
4.3. Treatment duration, relapse risk factors, long term
outcomes
 The remission rate following 2 years of treatment is
around 30% in children vs 40-60% in adults, meaning
the relapse rate is generally higher in children.

 Studies in children have shown that age (early age),

goiter size (large goiter), the initial severity of the
disease (based on serum T4 concentrations and anti-
TSH receptor autoantibody levels at diagnosis and
during progression), the time required to achieve
euthyroidism and the duration of initial medical
treatment were all factors predictive of relapse in
Graves’ disease.
4.4. Long term outcomes
 Long term outcomes depend on the potential
remission of the disease and the type of
treatment used.

 In addition, some patient may also develop

secondary autoimmune hypothyroidism.

 Long term follow-up care is requires, escpecially

in young girls and before any future pregnancies,
due to the risk of fetal and neonatal
hyperthyroidism induced by persistent high
levels of stimulating TSH receptor antibodies.
 Indication for a radical treatment can arise in
cases of :
◦ Contraindication to antithyroid agents
◦ Poorly controlled hyperthyroidism due to lack of
compliance
◦ Relapse despite prolonged medical treatment
◦ A request made by the family and child for personal
reasons
5.1. Surgery
 When radical treatment is required, surgery is the
treatment of choice in children under 5 years of
age (radioactive iodine is contraindicated).

 Surgery is required if the goiter is very large

(>80g) or is causing compression, if
thyrotoxicosis is severe and accompanied by
neurological symptoms, if the patient is suffering
from severe thyroid eye disease, or in cases
where conventional iodine treatment is
contraindicated.
5.1. Surgery
 In order to reduce the risk of recurrence, surgery
should remove the entirety of the majority
thyroid.

 In cases of partial or subtotal thyroidectomies,

the risk of recurrence is estimated to be 10-15%.

 The patient must be euthyroidism at the time of

surgey and Lugol administration for 10 days priot
to the operation will optimize conditions for the
surgical procedure by limiting the vascularization
of the thyroid.
5.2. Radioactive iodine treatment
 Radioactive iodine treatment is increasingly
used in Europe in preference to surgery.

 It is contraindicated :
◦ Expressly in children under 5 years of age (due to
the sensitivity of tissues to radiation).
◦ In relative terms for pre-pubescent children.
◦ For large goiters over 80g in mass.
5.2. Radioactive iodine treatment
 The objective of treatment with radioactive
iodine is to use an ablative dose to achieve
hypothyroidism given the risk of secondary
thyroid cancer.
5.2.1. Early side effects
 Local pain possible in the week following treatment
(less than 10%)

 Unlike in adults, given the extremely rare nature of

severe thyroid eye disease, preventive corticosteroid
therapy is not systematic
5.2.2. Long term risks
 The theroretical risk of secondary cancer
remains unresolved.

 Therefore, radioactive iodine treatment

currently appears to be an effective and safe
second-line treatment in childrena and an
alternative to surgery.